Hepatitis B virus mutants, reagents and methods for detection

Abstract

Mutant Hepatitis B Virus (HBV) nucleic acid sequences useful for a variety of diagnostic and therapeutic applications, kits for using the HBV nucleic acid sequences, HBV immunogenic particles, and a method for producing antibodies to HBV. Also provided are methods for producing antibodies, polyclonal or monoclonal, from the HBV nucleic acid sequences.

What is claimed is: 
     
       1. A purified polypeptide comprising the sequence of a mutant hepatitis B virus surface antigen (HBsAG) "a" determinant, in which the mutation is insertion of the amino acids Asn and Thr between positions 122 and 123 of the HBsAG sequence. 
     
     
       2. The purified polypeptide of claim 1, produced by expression of a recombinant nucleic acid. 
     
     
       3. The purified polypeptide of claim 1, produced by chemical synthesis. 
     
     
       4. A method for detecting HBV antibodies in a test sample, comprising: a. contacting a test sample suspected of having said antibodies with the polypeptide of claim 1, for a time and under conditions sufficient to allow antibody/antigen complexes to form; and   b. detecting the antibody/antigen complexes which contain the polypeptide.   
     
     
       5. A kit for determining the presence of mutant hepatitis B virus antigen or antibody, comprising a container and the polypeptide of claim 1. 
     
     
       6. The kit of claim 5, wherein the polypeptide is attached to a solid phase. 
     
     
       7. An immunogenic composition comprising the polypeptide of claim 1, optionally linked to a suitable carrier, and a pharmaceutically acceptable excipient. 
     
     
       8. A method for producing antibodies to a mutant hepatitis B virus, comprising administering to a host the composition of claim 7. 
     
     
       9. An isolated or purified immunogenic particle, comprising a polypeptide having an amino acid sequence capable of forming a particle when produced in a host cell, and an epitope of a mutant HBV, wherein said epitope comprises a modified "a" antigenic determinant wherein the modification is insertion of the amino acids Asn and Thr between positions 122 and 123 of the HBsAg sequence. 
     
     
       10. The immunogenic particle of claim 9, wherein the amino acid sequence capable of forming a particle is the amino acid sequence of hepatitis B surface antigen. 
     
     
       11. An immunogenic composition comprising the particle of claim 9 and a pharmaceutically acceptable excipient.